Alterations in CNS function due to developmental involvement have long been speculated; however, only in recent years have possible causes been identified. Among these (viral, irradiation, chemical, immunological, genetic), nutrition is most subtle and likely most prevalent. Furthermore, it is the most easily controlled given that knowledge is available concerning food intake, particularly during the critical periods. Minimal brain damage (MBD) is not easily evaluated in society and is particularly applicable to animal models. With this grant the changes in the cerebellar cortex of the malnourished rat model will be studied. Various degrees of protein restriction in a normal caloric diet will serve to test specific cerebellar modifications. The changes in the cerebellar elements and synaptic connections in the cerebellar cortex will be quantitatively evaluated to determine the alterations which occur in the circuitry under these conditions. Quantitation of granule cells, basket-stellate cells, molecular and granular layer synaptic contacts and volume of the layers in the cerebellum will be determined by computerized recording at the light or electron microscopic level. Synapses which cannot be distinguished by the semi-automatic system will be defined by ratio sampling and then by adjusting the total number. The volume of the respective layers together with the sample counts gives the total number of structures in order that the change can be fully evaluated. Since the cerebellum is most markedly affected, this study should yield important results from hard data that can be correlated with the malnutrition state and, ultimately, with motor function. Bibliographic references: LLinas, R. and Hillman, D.E. A multipurpose tridimensional reconstruction computer system for neuroanatomy. In: Golgi Centennial Symposium: Perspectives in Neurobiology, ed.by M. Santini. New York: Raven Press, 1975. Hillman, D.E., Llinas, R. and Chujo, M. Automatic and semiautomatic analysis of nervous system structure. In: Computer Analysis of Neuronal Structures, ed. by R.D. Lindsay. Univ. of Calif., 1975.